This research proposal focuses on the immunobiology of the human pulmonary alveolar macrophage (PAM), particularly on the role of PAM subpopulation in normal physiology and in pulmonary disease. PAM subsets will be isolated by size, density and counterflow centrifugation, as well as through the fluorescent activacted cell sorter using monoclonal anti-PAM antibodies. Isolated subsets will be studied as to number and avidity of Fc (IgG and IgE) and complement (C3 receptors, corticosteroid sensitivity of Fc gamma and C3 receptors and number of corticosteroid surface receptors. The sensitivity of PAM subsets to stimulatory compounds, including levamisole and low molecular weight peptides will also be examined. These functional studies will be performed in consort with morphologic studies, including scanning and transmission electron microscopy. The ability of PAM subsets to respond to chemotactic stimuli, to recognize the benign and malignant lymphoid cell surface and to support Concanavalin A mediated mitogenesis will also be examined. Comparative studies using peripheral blood monocytes and monocyte cultures will be employed. PAM subpopulations are probably intricately involved in pulmonary host defense, antigen processing and immunoregulatory systems. Aberration in one or more subset functions may play a role in the pathophysiology of immunologic disease of the lung. Three pulmonary disease states will be studied in regard to specific PAM function: Idiopathic pulmonary fibrosis with circulating immune complexes, bronchopulmonary aspergillosis with increased circulating IgE and hypersensitivity pneumonitis. A detailed analysis of PAM subpopulations should help to define the role of the pulmonary macrophage in the pathophysiology of lung disease and help to delineate the rationale for pharmacologic intervention.